[Isoelectric focusing in neurological diagnosis]. / Die isoelektrische Fokussierung in der neurologischen Diagnostik.

The cerebrospinal fluid (CSF) of 1673 neurological patients in whom conventional agar electrophoresis failed to provide conclusive results was analyzed by isoelectric focusing (IEF). The primary aim of the study was not to analyze the frequency of oligoclonal immunoglobulins in the CSF of patients with inflammatory diseases of the central nervous system (CNS) but to answer the question how often, and in which particular disturbances, gamma-globulin changes typical of inflammatory processes are found in conditions which do not primarily belong to the group of inflammatory CNS diseases. It is shown that oligoclonal IgG bands in these circumstances are not common but did occasionally occur in most diagnostic groups. Results suggest increased frequency in certain groups such as Guillain-Barré polyradiculitis and in various neoplastic disorders. The diagnostic difficulties resulting from these findings and the advantages of IEF over the more generally favoured "Ig-index" are discussed. In addition, we report on the occasional appearance of monoclonal IgG gammopathies either associated with inflammatory CNS reactions or - more frequently - as an isolated and unexplained finding.

Serum proteins and zinc as parameters to monitor the health of children in a rural Tanzanian community.

Total protein concentration, zinc, prealbumin, albumin, alpha-1-, alpha-2-, beta- and gammaglobulin concentrations were measured in serum samples collected in three successive years (1982, 1983 and 1984) from children (1 month-15 years) of Kikwawila village, Tanzania. The analysis of a total of 1590 serum samples provided the baseline data for children living in a rural Tanzanian community. The total protein values and the concentrations of betaglobulin were within the range described for Caucasians. Albumin, prealbumin, alpha-1- and alpha-2-globulin concentrations were below these standard values. On the other hand the gammaglobulin concentration was twice as high. The concentrations of total protein, gammaglobulin and prealbumin correlated with age. From 1982 to 1983 a significant decrease of most of the serum components (incl. zinc) was observed, although in children older than 2 years the alpha-1-globulins increased. All values increased again from 1983 to 1984, except for the zinc concentration, which decreased further. The individual fluctuations were analysed by comparing paired values for the children participating in the period 1982-1983, or 1983-1984. The proportion of children showing large fluctuations, sometimes exceeding the selected limits of tolerance, was larger in the period 1982-1983 than 1983-1984. This was consistent with the overall pattern found for all children. The prealbumin level, which has been postulated to be an indicator for malnutrition or borderline malnutrition, was analysed in detail. The values were far below normal values (200-300 mg/l), reaching a plateau with 130 mg/l among 4-6-year-old children. The individual fluctuations indicated a decrease from 1982 to 1983, which was considerable both in terms of the proportion of children showing a decrease (55%) and in the magnitude of the decrease. There was an increase from 1983 to 1984 but this increase did not compensate for the loss in 1983. Prealbumin concentrations showed a slight trend towards decreased values with stunting and wasting. No direct correlation was found between the other biochemical parameters and the parasite or anthropometric data collected at the same time. It was difficult to establish direct relationships between the biochemical parameters, which mainly indicate the health status of the child at the time-point of the survey, and anthropometric parameters which reflect the history of the individual over a long period. No direct correlation could be established between the biochemical parameters and the parasitological data.(ABSTRACT TRUNCATED AT 400 WORDS)

[Perinatal relation of the blood-cerebrospinal fluid barrier and its effect on protein composition of the cerebrospinal fluid]. / Die perinatalen Verhältnisse der Blut-Liquorschranke und ihr Einfluss auf die Proteinzusammensetzung des Liquors.

The lumbar spinal fluid of 70 infants aged 238-461 days after conception was examined for total protein with the Cu-Folin-differential test, and for variation of single CSF proteins as a function of developmental age using agar gel electrophoresis. In the early stages of development all CSF fractions as well as total protein are increased compared with adult persons. The absolute amounts decrease after birth more or less rapidly (partly exponentially) and reach a minimum between the 52nd and 57th week of development (prealbumin and beta 1-globulin somewhat earlier, albumin somewhat later). Except for beta 1-globulin this minimum is always lower than the normal adult values. There seems to be a linear correlation between the logarithm of the total protein (also of certain single proteins) and the gestational age over a wide range of development. The behaviour of the haptoglobin and immunoglobulin fractions demonstrates especially well that many independent factors may simultaneously influence the concentration of the CSF proteins (e.g. plasma content of proteins, permeability of the blood/brain or blood/CSF barrier) and that these factors themselves depend on both the developmental state (gestational age) and chronological age (birth). This study, in agreement with the results of other authors suggests that in human neonates the reference range of those CSF parameters which depend on barrier conditions should be related to the gestational age rather than to the chronological age.

[Hyperhaptoglobinemia in plasmacytoma and amyloidosis]. / Hyperhaptoglobinämie bei Plasmozytom und Amyloidose.

Massive hyperhaptoglobinaemia (more than 8 g/l) was seen in a 58-year-old female patient with plasmocytoma and amyloidosis. In the literature, hyperhaptoglobinaemias of up to the three- or fourfold of the upper normal limit have been reported. However, they are very rare. In the present case it might be speculated that extrahepatic formation of haptoglobin occurred within paraproteinaemia of plasmocytoma.

[Determination of protein in cerebrospinal fluid: comparison of the Coomassie-Blue method and the Cu-Folin differential test]. / Bestimmung von Protein im Liquor: Vergleich der Coomassie-Blau-Methode mit dem Cu-Folin-Differentialtest.

Comparison of within-run and between-day imprecision of protein assays using CSF controls as well as 96 random CSF samples from the routine laboratory shows that the Cu-Folin differential test and the Coomassie-Brilliant-Blue method from Bio-Rad are equally suited to total protein determination in cerebrospinal fluid. Problems possibly arising with very low concentrations of CSF or urine protein and the influence of some drugs often used in the neurological clinic are presented and discussed.

Trace elements in whole blood of multiple sclerosis.

Fe, Zn, and Cu were determined by atomic absorption spectrometry in samples of whole blood after weighing and wet ashing with HNO3. 35 healthy persons were compared with 119 multiple sclerosis (MS) patients and 13 patients with other diseases of the CNS. The values from normal persons are in full agreement with those cited in the literature, men showing a significantly higher level of Fe than women, whereas for Zn and Cu there is no significant sex difference. In comparison with the reference group the patients show no difference at all for Fe and only a minor one for Cu, but Zn values are greatly increased in MS patients (by 25-75%). The increase is higher in the relapsing form of MS than in the chronic form, suggesting some connection with the activity of the disease. On the other hand, the duration of the illness and (implicitly) the age of the patient seem to be unimportant. As patients with other diseases of the CNS show a similar though somewhat smaller increase, we conclude that Zn elevation in whole blood is not a feature specific for MS. From the present results, however, we cannot decide if such deviations are causally connected with affections of the CNS or if they are only a concomitant manifestation.

[Vitamin status in diabetic neuropathy (thiamine, riboflavin, pyridoxin, cobalamin and tocopherol)]. / Untersuchungen zum Vitamin-Status bei diabetischer Neuropathie (Thiamin, Riboflavin, Pyridoxin, Cobalamin und Tocopherol).

Investigations on the vitamin pattern of diabetic neuropathy: thiamine, riboflavin, pyridoxine, cobalamin and tocopherol. The contents of the vitamins mentioned above have been measured in the blood of 119 patients (53 diabetic neuropathies, 66 diabetics without neuropathy). The incidence of neuropathy shows a strong correlation with the duration of the diabetic state, but not with sex, nor with concomitant diseases such as adipositas, hypertension, heart and circulatory diseases, except retinopathia diabetica. Most of the diabetics in our study are well supplied with vitamins B1, B2, and E; B6 and B12 are occasionally low, but there is no statistically relevant difference between diabetic controls and neuropathies. Adipose patients have neither a markedly different vitamin content nor a different calory uptake from non-adipose patients. A general trend towards reduced total calory uptake is seen in old age, men (lower protein intake) and women (lower carbohydrate intake) obviously differing somewhat in their habits. The influence of therapy on the vitamin pattern is not clear cut, except for patients under diet and biguanide-therapy showing a higher proportion of low or subnormal B12 values. The increased frequency of neuropathies in patients treated with sulfonyl-urea approaches only the limits of significance and needs further investigations.

[Isoelectric focusing and agar electrophoresis of the cerebrospinal fluid in neurologic patients]. / Isoelektrische Fokussierung und Agar-Elektrophorese des Liquor cerebrospinalis bei neurologischen Patienten.

Both isoelectric focusing and routine agar gel electrophoresis have been carried out on the CSF, and in some cases also on the corresponding serum, from 452 control subjects and patients with neurological diseases among whom cases with multiple sclerosis (MS) predominated. Comparison of the results confirms the superiority of electrofocusing over gel electrophoresis for the evaluation of oligoclonal immune reactions of the CNS. Over 90% of the MS patients showed discontinuous subfractionation of the gamma-globulins, mostly confined to the CSF, whereas with agar gel electrophoresis an identical effect could be seen only in about 60% of the same patients. Of special interest is the fact that by isoelectric focusing an additional 20% of MS patients whose gamma-globulin content, cell count and plasma cell findings in the CSF are within normal limits show oligoclonal CSF immune reactions. Thus, after appropriate screening by routine electrophoresis to reduce the number of analyses, the relatively laborious method of isoelectric focusing is an effective addition to the usual CSF investigations.

[Total proteins and electrophoretic protein fractions in the juvenile cerebrospinal fluid]. / Totalprotein und elektrophoretische Proteinfraktionen des Liquors im Kindesalter.

In the CSF of 933 children and young people, total protein (T.P.) and the protein fractions (separated by electrophoresis were found to be definitely dependent on the age of the child, both in patients and normal controls. The highest values of T.P. are found in the first weeks of life. A steep decrease to the lowest values in the second to third year is followed by a slow increase over the next decade until the adult range is reached at the age of about 15 years. Because of the immature blood-CSF barrier and/or blood-brain barrier, the protein fractions of the newborn show a transsudative electrophoresis pattern with high albumin and gamma-globulin, but low prealbumin. Some weeks later, the pattern has completely changed: a transient elevation of beta 1-globulin, followed by elevation of the prealbumin and the alpha 2-fractions, is correlated with a decrease in the albumin, tau- and gamma-globulin fractions. At the age of 12--16 years, adult conditions are nearly reached. When children with various neurological diseases are compared with normal controls of identical age, the pattern of deviations is generally very similar to that observed in adults with the same diseases.

The activity of gamma-glutamyl transferase in the serum of multiple sclerosis and other neurological diseases.

1. In the sera of 142 neurological patients, including 35 cases with multiple sclerosis (MS), and 20 normal controls the gamma-glutamyltransferase (gamma-GT) activity was determined. The result of this investigation was compared with the "combined hippuric acid test" formely often used in MS patients. 2. The MS patients are the only group which significantly differs from the normal controls. There are also small differences between them and some of the other neurological patient groups. About one-third of the MS patients show moderately pathological serum activities. On the other hand, patients with a definite liver affection, especially chronic alcoholics, regularly show an even more important elevation of the values, which makes this test a sensitive tool for the screening of alcohol-induced liver intoxications. 3. Although the gamma-GT test in not quite as sensitive in indicating organic defects in MS patients, it seems to reflected a disturbed liver function in the same way as the more complicated "combined hippuric acid test". It may therefore be used as a simple tool of finding and following up organic defects in MS patients.

The course of multiple sclerosis cases with extremely high gamma-globulin values in the cerebrospinal fluid.

40 selected cases of multiple sclerosis (MS) with extremely high gamma-globulin values in the cerebrospinal fluid (CSF) (over 25 rel%, upper normal limit 7.5 rel%) were matched with the same number of MS patients with normal CSF findings. Surprisingly, no definite relationship could be shown between the amount of CSF gamma-globulins and the various clinical criteria in MS, such as age, type of progression, duration of illness, remission, extent of plaques and gravity of the disease.

[Cerebrospinal fluid protein electrophoresis in non-inflammatory central nervous system diseases]. / Liquirprotein-Elektrophoresen bei nicht-entzündlichen Erkrankungen des Zentralnervensystems

Cerebrospinal fluids (CSF) (N = 365) from patients with non-inflammatory diseases of the central nervous system were analyzed for protein distribution by agar gel microelectrophoresis. After subdivision into diagnostically well defined groups, these patients were compared with 79 normal controls. Most of the diseases investigated were found to follow the "plasma-type" pattern. In some of them the deviations from normal were so extensive that a CSF-protein pattern similar to the "acute-phase reaction" in the serum occurred. Moreover, the following characteristics were found: a considerable increase in total protein and the gamma-globulin fractions in neurinomas; a reproducible increase in the alpha1-globulins in metastases of the central nervous system; and a statistically significant difference of CSF protein findings between male and female patients with protrusion of lumbar intervertebral discs.

[Behavior of cerebrospinal fluid proteins in degenerative diseases]. / Das Verhalten der Liquorproteine bei degenerativen Erkrankungen

132 cerebrospinals fluids from patients with degenerative diseases of the central nervous system have been analyzed for protein distribution in agar gel electrophoresis. After subdivision into diagnostically well defined groups these patients were compared with 48 with metabolic and psychiatric diseases and with 79 normal controls. The majority of diagnostic groups showed a tendency to permeability impairment. Other outstanding deviations were not found, except for single cases which were not statistically typical of the groups as a whole. However, the "degenerative type" of proteinogram emphasized in the literature predominated not only in the degenerative groups but also in certain other diseases with destruction of central nervous tissue which do not belong to the degenerative diseases in the strict sense. On the other hand, there are some degenerative subgroups without this "typical" electrophoretic pattern. There would thus appear to be grounds for amending the term "degenerative" into "tissue destroying" or "atrophic type", to avoid misinterpretation.

Absolute or relative values in csf electrophoresis? An evaluation of the gamma-globulins in multiple sclerosis and other neurological diseases.

The frequencies of pathological results in 143 CSF samples of MS patients from the years 1964-1967, and 206 samples from 1968-1973 were compared after agar electrophoresis and cytological differentiation. As they were in good agreement, the two series were combined into one group of 349 MS patients for further comparison with three groups with other neurological diseases (inflammatory, neoplastic and vascular brain affections). Although the absolute gamma-globulin values (mg/l) are somewhat more frequently pathological than the relative values (rel%), they also correlate significantly with total protein and, therefore, do not offer a criterion with a diagnostic value of its own. From them - as from the total protein - a pathological CSF state cna be concluded, but no discrimination between MS and other diseases of the central nervous system is possible. The relative percent values for the gamma-globulins are much less correlated with total protein in all the 4 groups compared; consequently, they represent a more specific criterion for differential diagnosis.